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A first comprehensive analysis of Transcribed Ultra Conserved Regions uncovers important regulatory functions of novel non-coding transcripts in gliomas

Myron K Gibert Jr, Ying Zhang, Shekhar Saha, Pawel Marcinkiewicz, Collin Dube, Kadie Hudson, Yunan Sun, Sylwia Bednarek, Bilhan Chagari, Aditya Sarkar, Christian Roig-Laboy, Natalie Neace, Karim Saoud, Initha Setiady, Farina Hanif, Pankaj Kumar, Benjamin Kefas, Roger Abounader
doi: https://doi.org/10.1101/2023.09.12.557444
Myron K Gibert Jr
1University of Virginia Departments of Microbiology, Immunology & Cancer Biology, Charlottesville, VA, 22908, USA
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Ying Zhang
1University of Virginia Departments of Microbiology, Immunology & Cancer Biology, Charlottesville, VA, 22908, USA
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Shekhar Saha
1University of Virginia Departments of Microbiology, Immunology & Cancer Biology, Charlottesville, VA, 22908, USA
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Pawel Marcinkiewicz
1University of Virginia Departments of Microbiology, Immunology & Cancer Biology, Charlottesville, VA, 22908, USA
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Collin Dube
1University of Virginia Departments of Microbiology, Immunology & Cancer Biology, Charlottesville, VA, 22908, USA
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Kadie Hudson
1University of Virginia Departments of Microbiology, Immunology & Cancer Biology, Charlottesville, VA, 22908, USA
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Yunan Sun
1University of Virginia Departments of Microbiology, Immunology & Cancer Biology, Charlottesville, VA, 22908, USA
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Sylwia Bednarek
1University of Virginia Departments of Microbiology, Immunology & Cancer Biology, Charlottesville, VA, 22908, USA
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Bilhan Chagari
1University of Virginia Departments of Microbiology, Immunology & Cancer Biology, Charlottesville, VA, 22908, USA
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Aditya Sarkar
1University of Virginia Departments of Microbiology, Immunology & Cancer Biology, Charlottesville, VA, 22908, USA
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Christian Roig-Laboy
1University of Virginia Departments of Microbiology, Immunology & Cancer Biology, Charlottesville, VA, 22908, USA
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Natalie Neace
1University of Virginia Departments of Microbiology, Immunology & Cancer Biology, Charlottesville, VA, 22908, USA
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Karim Saoud
1University of Virginia Departments of Microbiology, Immunology & Cancer Biology, Charlottesville, VA, 22908, USA
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Initha Setiady
1University of Virginia Departments of Microbiology, Immunology & Cancer Biology, Charlottesville, VA, 22908, USA
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Farina Hanif
1University of Virginia Departments of Microbiology, Immunology & Cancer Biology, Charlottesville, VA, 22908, USA
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Pankaj Kumar
4Department of Public Health Sciences and Bioinformatics Core, Charlottesville, VA, 22908, USA
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Benjamin Kefas
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Roger Abounader
1University of Virginia Departments of Microbiology, Immunology & Cancer Biology, Charlottesville, VA, 22908, USA
2Department of Neurology, Charlottesville, VA, 22908, USA
3Department of Cancer Center, Charlottesville, VA, 22908, USA
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  • For correspondence: ra6u@virginia.edu
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ABSTRACT

Transcribed Ultra-Conserved Regions (TUCRs) represent a severely understudied class of putative non-coding RNAs (ncRNAs) that are 100% conserved across multiple species. We performed the first-ever analysis of TUCRs in glioblastoma (GBM) and low-grade gliomas (LGG). We leveraged large human datasets to identify the genomic locations, chromatin accessibility, transcription, differential expression, correlation with survival, and predicted functions of all 481 TUCRs, and identified TUCRs that are relevant to glioma biology. Of these, we investigated the expression, function, and mechanism of action of the most highly upregulated intergenic TUCR, uc.110, identifying it as a new oncogene. Uc.110 was highly overexpressed in GBM and LGG, where it promoted malignancy and tumor growth. Uc.110 activated the WNT pathway by upregulating the expression of membrane frizzled-related protein, by sponging the tumor suppressor miR-544. This pioneering study shows important roles for TUCRs in gliomas and provides an extensive database and novel methods for future TUCR research.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted September 18, 2023.
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A first comprehensive analysis of Transcribed Ultra Conserved Regions uncovers important regulatory functions of novel non-coding transcripts in gliomas
Myron K Gibert Jr, Ying Zhang, Shekhar Saha, Pawel Marcinkiewicz, Collin Dube, Kadie Hudson, Yunan Sun, Sylwia Bednarek, Bilhan Chagari, Aditya Sarkar, Christian Roig-Laboy, Natalie Neace, Karim Saoud, Initha Setiady, Farina Hanif, Pankaj Kumar, Benjamin Kefas, Roger Abounader
bioRxiv 2023.09.12.557444; doi: https://doi.org/10.1101/2023.09.12.557444
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A first comprehensive analysis of Transcribed Ultra Conserved Regions uncovers important regulatory functions of novel non-coding transcripts in gliomas
Myron K Gibert Jr, Ying Zhang, Shekhar Saha, Pawel Marcinkiewicz, Collin Dube, Kadie Hudson, Yunan Sun, Sylwia Bednarek, Bilhan Chagari, Aditya Sarkar, Christian Roig-Laboy, Natalie Neace, Karim Saoud, Initha Setiady, Farina Hanif, Pankaj Kumar, Benjamin Kefas, Roger Abounader
bioRxiv 2023.09.12.557444; doi: https://doi.org/10.1101/2023.09.12.557444

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